Abstract

Abstract BACKGROUND AND AIMS Protein energy wasting (PEW) is currently considered as one of the most important and independent predictors of an unfavourable prognosis in patients receiving haemodialysis treatment. The insufficient intake of nutrients and energy can be related to the ̏leaky gut̎ syndrome. Zonulin secretion has been shown to be dependent and is followed by an increase in gut permeability secondary to the disassembly of the protein ZO-1 from the tight junctional complex. Thus, the serum zonulin level may be considered as a biomarker of impaired intestinal barrier function. Тhe aim of our study was to evaluate the relationship between PEW and intestinal permeability, estimated by the level of serum zonulin, in patients receiving hemodialysis treatment. METHOD This was a case-control study involving 148 participants (123 haemodialysis patients and 25 control subjects). Patients diagnosed with infectious illness, unstable blood pressure, clinically active gastrointestinal disease, past history of abdominal operation and taking antibacterial, nonsteroidal anti-inflammatory and laxatives drugs were excluded. The presence of PEW was carried out by the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria, which requires that patients meet at least one criterion in three of the four proposed categories: altered biochemical laboratory tests, loss of body mass, loss of muscle mass and decreased protein or energy intake. Bioimpedance measurements were obtained with an InBody720 equipment (Biospace, Korea). Plasma concentration of zonulin was assessed by ELISA using commercially available kit (BlueGene Biotech, Shanghai, China). RESULTS This study included 123 (75 men and 48 women) clinically stable patients undergoing haemodialysis in our centre. The average age was 59 years (49–67 years), and the mean duration of dialysis treatment was 36 (24–53) months. Given the absence of generally accepted reference values for serum zonulin levels, haemodialysis patients parameters were compared with the data of 25 healthy volunteers (13 men and 12 women) with an average age of 49 years (41.5–55). Zonulin level was significantly higher in the haemodialysis patients as compared with the healthy control 236.1 (190.3–310.9) ng/mL versus 190.6 (156.3–231.4) ng/mL, P < 0.01. Of the total population, 27 patients (22%) met the diagnostic criteria of PEW. The subgroup analysis between those with PEW and without PEW showed a statistically significant difference in serum zonulin concentration: 311.1 (282.6–406) versus 223.7 (182.8–271) ng/mL, respectively, P < 0.0001. Among subjects with PEW, there was a significant correlation between zonulin level and serum albumin (r = –0.404; P = 0.018), body mass index (r = –0.281; P = 0.021), body fat mass index (r = –0.55; P = 0.019), skeletal muscle mass index (r = –0.395; P = 0.007), erythrocyte sedimentation rate (r = 0.199; P = 0.04) and C-reactive protein (r = 0.642; P < 0.001). In the meantime, there was no significant interaction between zonulin and age, duration of dialysis treatment, Kt/V, shoulder muscle circumference, triceps skinfold, haemoglobin, total cholesterol, transferrin and lymphocyte levels (all P-values > 0.05). CONCLUSION Our study shows that PEW in haemodialysis patients could be associated with the increased intestinal permeability. Thus, different strategies that attenuate intestinal barrier disruption may be a potential therapeutic tool for the prevention and treatment of PEW. Limitation of the present study was the limited sample of participants, which probably influenced the significance of statistical tests. Further clinical studies are needed in a larger population as well as their prospective follow-up to enhance the understanding of this topic.

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