Assessment of Gut leakage Induced Systemic Inflammation in Children on Chronic Hemodialysis

Ragia Said; Maged A. El Wakeel; Hasanin Mohamed; Ghada El Kassas; Ahmed F. Amer; May M. Abdel Hamid; Ayman Armaneos; Salwa Refat El-Zayat; Nevein N. Fadl

doi:10.3889/oamjms.2022.8465

Authors

Ragia Said Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
Maged A. El Wakeel Department of Child Health, National Research Centre, Giza, Egypt https://orcid.org/0000-0003-2634-8577
Hasanin Mohamed Department of Pediatric, National Research Centre, Giza, Egypt
Ghada El Kassas Department of Child Health, National Research Centre, Giza, Egypt https://orcid.org/0000-0002-5258-8446
Ahmed F. Amer Department of Child Health, National Research Centre, Giza, Egypt
May M. Abdel Hamid Department of Child Health, National Research Centre, Giza, Egypt https://orcid.org/0000-0002-9138-0429
Ayman Armaneos Department of Child Health, National Research Centre, Giza, Egypt https://orcid.org/0000-0002-9127-4415
Salwa Refat El-Zayat Department of Medical Physiology, National Research Centre, Giza, Egypt
Nevein N. Fadl Department of Medical Physiology, National Research Centre, Giza, Egypt https://orcid.org/0000-0002-0712-5637

DOI:

https://doi.org/10.3889/oamjms.2022.8465

Keywords:

Hemodialysis-intestinal permeability, Systemic inflammation, Zonulin-children

Abstract

BACKGROUND: Children with chronic kidney disease (CKD) are at high risk to develop GIT complications such as intestinal wall edema and increased permeability which contributes to chronic systemic inflammation that increases morbidity and mortality burden.

AIM: This study aim was to show the relationship between inflammation and increased intestinal permeability in children on hemodialysis (HD).

METHODS: The study included 50 children with CKD on regular HD of variable duration; their age range was (5−16) years and 40 controls. They were followed up at Nephrology clinic- Eldemerdash hospital. Complete history taking, physical examination were done. Laboratory measurement in the form of zonulin, tumor necrosis factor-alpha (TNF-alpha), high sensitive C-reactive protein (hs-CRP), and alpha1-antitrypsin (AAT) were quantified in serum by ELISA method.

RESULTS: There was a highly significant decrease in anthropometric measures (weight, height and BMI) and their corresponding z score in cases compared to controls with p ≤ 0.001. Furthermore, there was significant increase of levels of zonulin, TNF-alpha, AAT, and hs-CRP in cases compared to controls with p value of 0.009, 0.001, 0.002, and 0.003, respectively. There was significant positive correlation between zonulin and (TNF-alpha, AAT, hs-CRP, and creatinine) with P values (0.003, 0.001, 0.001, and 0.001), respectively. Zonulin is negatively correlated with weight for age Z score (WAZ) and height with p value (0.01 and 0.018), respectively. TNF-alpha and hs-CRP were negatively correlated with WAZ with P-values of 0.02 and 0.01, respectively.

CONCLUSION: Children with CKD on chronic hemodialysis had elevated levels of zonulin, TNF-alpha, hs-CRP, and AAT which reflects gut permeability induced systemic inflammatory state.

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References

Cobo G, Lindholm B, Stenvinkel P. Chronic inflammation in end-stage renal disease and dialysis. Nephrol Dial Transplant. 2018 Oct 1;33(Suppl 3):iii35-40. https://doi.org/10.1093/ndt/gfy175 PMid:30281126 DOI: https://doi.org/10.1093/ndt/gfy175

Colombo I, Aiello-Battan F, Elena R, Ruiz A, Petraglia L, Musso CG. Kidney-gut crosstalk in renal disease. Irish J Med Sci. 2020;190(3):1205-12. https://doi.org/10.1007/s11845-020-02437-7 PMid:33216316 DOI: https://doi.org/10.1007/s11845-020-02437-7

Khoury T, Tzukert K, Abel R, Rmeileh AA, Levi R, Ilan Y. The gut-kidney axis in chronic renal failure: A new potential target for therapy. Hemodial Int. 2017;21(3):323-34. https://doi.org/10.1111/hdi.12486 PMid:27634464 DOI: https://doi.org/10.1111/hdi.12486

Said RM, El Wakeel MA, El-Kassas GM, Mostafa HH, Kamhawy AH, Galal EM, et al. Protein energy wasting in a sample of Egyptian children on regular hemodialysis: Relation to anorexigenic hormones. Open Access Maced J Med Sci. 2020;8(B):658-65. https://doi.org/10.3889/oamjms.2020.4981 DOI: https://doi.org/10.3889/oamjms.2020.4981

Klaus DA, Motal MC, Burger-Klepp U, Marschalek C, Schmidt EM, Lebherz-Eichinger D, et al. Increased plasma zonulin in patients with sepsis. Biochem Med (Zagreb). 2013;23(1):107-1. https://doi.org/10.11613/bm.2013.013 PMid:23457771 DOI: https://doi.org/10.11613/BM.2013.013

Lau WL, Vaziri ND. The leaky gut and altered microbiome in chronic kidney disease. J Ren Nutr. 2017;27(6):458-61. https://doi.org/10.1053/j.jrn.2017.02.010 PMid:29056165 DOI: https://doi.org/10.1053/j.jrn.2017.02.010

Lin TY, Wu PH, Lin YT, Hung SC. Gut dysbiosis and mortality in hemodialysis patients. NPJ Biofilms Microbiomes. 2021;7(1):20. https://doi.org/10.1038/s41522-021-00191-x PMid:33658514 DOI: https://doi.org/10.1038/s41522-021-00191-x

Long J, Vela Parada X, Kalim S. Protein carbamylation in chronic kidney disease and dialysis. Adv Clin Chem. 2018;87:37-67. https://doi.org/10.1016/bs.acc.2018.07.002 PMid:30342712 DOI: https://doi.org/10.1016/bs.acc.2018.07.002

March DS, Graham-Brown MP, Stover CM, Bishop NC, Burton JO. Intestinal barrier disturbances in haemodialysis patients: Mechanisms, consequences, and therapeutic options. Biomed Res Int. 2017;2017:5765417. https://doi.org/10.1155/2017/5765417 PMid:28194419 DOI: https://doi.org/10.1155/2017/5765417

El Wakeel MA, El-Kassas GM, Ahmed GF, Ali WH, Elsheikh EM, El-Zayat SR, et al. Fecal markers of environmental enteric dysfunction and their relation to faltering growth in a sample of Egyptian children. Open Access Maced J Med Sci. 2021;9(B):1117-22. https://doi.org/10.3889/oamjms.2021.7029 DOI: https://doi.org/10.3889/oamjms.2021.7029

Sánchez-Alcoholado L, Ordóñez R, Otero A, Plaza-Andrade I, Laborda-Illanes A, Medina JA, et al. Gut Microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int J Mol Sci. 2020;21(18):6782. https://doi.org/10.3390/ijms21186782 PMid:32947866 DOI: https://doi.org/10.3390/ijms21186782

El-Kassas GM, El Wakeel MA, Elabd MA, Kamhawy AH, Atti MA, Abd El-Gaffar SA, et al. Vitamin D status in neonatal pulmonary infections: Relationship to inflammatory indicators. Open access Maced J Med Sci. 2019;7(23):3970-4. https://doi.org/10.3889/oamjms.2019.592 PMid:32165938 DOI: https://doi.org/10.3889/oamjms.2019.592

Sriwijitalai W, Wiwanitkit V. Ralstonia infection among hemodialysis patients: A summary. Saudi J Kidney Dis Transpl. 2019;30(3):749-50. https://doi.org/10.4103/1319-2442.261367 PMid:31249248 DOI: https://doi.org/10.4103/1319-2442.261367

Tanigasalam V, Bhat BV, Adhisivam, B, Sridhar MG, Harichandrakumar KT. Predicting severity of acute kidney injury in term neonates with perinatal asphyxia using urinary neutrophil gelatinase associated lipocalin. Indian J Pediatr. 2016;83(12- 13):1374-8. https://doi.org/10.1007/s12098-016-2178-z PMid:27299341 DOI: https://doi.org/10.1007/s12098-016-2178-z

El Wakeel M, El-Kassas G, Hashem S, Mohamed H, Ali W, Elkhatib AA, et al. Serum biomarkers of environmental enteric dysfunction and growth perspective in egyptian children. Open Access Maced J Med Sci. 2020;8(T2):246-53. https://doi.org/10.3889/oamjms.2020.7023 DOI: https://doi.org/10.3889/oamjms.2020.7023

Vancamelbeke M, Vermeire S. The intestinal barrier: A fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017;11(9):821-34. https://doi.org/10.1080/17474124.2017.1343143 PMid:28650209 DOI: https://doi.org/10.1080/17474124.2017.1343143

Wong J, Lenaerts K, Meesters DM, Olde Damink SW, van Eijk HM, Vilar E, et al. Acute haemodynamic changes during haemodialysis do not exacerbate gut hyperpermeability. Biosci Rep. 2019;39(4):BSR20181704. https://doi.org/10.1042/bsr20181704 PMid:30898976 DOI: https://doi.org/10.1042/BSR20181704

Yu J, Shen Y, Zhou N. Advances in the role and mechanism of zonulin pathway in kidney diseases. Int Urol Nephrol. 2021:53(10):2081-8. https://doi.org/10.1007/s11255-020-02756-9 PMid:33428167 DOI: https://doi.org/10.1007/s11255-020-02756-9

Elzaree FA, Shehata MA, El Wakeel MA, El-Alameey IR, AbuShady MM, Helal SI. Adaptive functioning and psychosocial problems in children with beta thalassemia major. Open access Maced J Med Sci. 2018;6(12):2337. https://doi.org/10.3889/oamjms.2018.367 PMid:30607187 DOI: https://doi.org/10.3889/oamjms.2018.367

Gupta A, Mantan M, Sethi M. Nutritional assessment in children with chronic kidney disease. Saudi J Kidney Dis Transpl. 2016;27(4):733-9. https://doi.org/10.4103/1319-2442.185235 PMid:27424690 DOI: https://doi.org/10.4103/1319-2442.185235

Goyal KK, Saha A, Sahi PK, Kaur M, Dubey NK, Goyal P, et al. Hepcidin and proinflammatory markers in children with chronic kidney disease: A case-control study. Clin Nephrol. 2018;89(5):363-70. https://doi.org/10.5414/cn109132 PMid:29451472 DOI: https://doi.org/10.5414/CN109132

Anders HJ, Andersen K, Stecher B. The intestinal microbiota, a leaky gut, and abnormal immunity in kidney disease. Kidney Int. 2013;83(6):1010-6. https://doi.org/10.1038/ki.2012.440 PMid:23325079 DOI: https://doi.org/10.1038/ki.2012.440

Ficek J, Wyskida K, Ficek R, Wajda J, Klein D, Witkowicz J, et al. Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. International Urol Nephrol. 2017;49(4):717-25. https://doi.org/10.1007/s11255-016-1495-5 PMid:28044237 DOI: https://doi.org/10.1007/s11255-016-1495-5

El Wakeel MA, El-Kassas GM, Hashem SA, Abouelnaga MW, Elzaree FA, Hassan M, et al. Potential role of oxidative stress in childhood obesity and its relation to inflammation. Biosci Res. 2018;15(4):3791-9.