Gut-derived uremic toxins and their role in accelerating cardiovascular events in chronic kidney disease
DOI:
https://doi.org/10.65327/kidneys.v14i4.561Keywords:
chronic kidney disease; uremic toxins; gut microbiota; cardiovascular disease; indoxyl sulfate; p-cresyl sulfate; cardiovascular risk factorsAbstract
Chronic kidney disease (CKD) is a long-lasting and progressive condition. It is caused by the
complicated buildup of many serum uremic toxins, some of which are made by the gut flora. Two uremic toxins, indoxyl sulfate and p-cresyl sulfate, have been shown to worsen cardiovascular disease and accelerate the progression of chronic kidney disease. These toxins harm the heart over time by causing the blood arteries swell, creating oxidative stress, and making the endothelium work poorly or not at all. The relationships between uremic toxins produced in the gastrointestinal tract and cardiovascular events in individuals with CKD remain inadequately defined, especially with prospective new biomarkers that could facilitate earlier diagnosis of cardiovascular events and the commencement of treatment. This aims to conduct a systematic review and research on cardiovascular risk factors associated with specific gutderived uremic toxins, with a particular focus on blood pressure, atherosclerosis, and arterial stiffness in individuals with CKD. This study aims to elucidate more definitions regarding the impact of these toxins on clinical events and the pathobiology of cardiovascular illnesses in individuals with chronic renal disease.
Furthermore, when examining these data, we will consider treatment strategies aimed at modifying
certain factors by targeting the microbiome to maintain positive clinical outcomes, as well as interventions
that inhibit the production of gut-derived uremic toxins to eliminate or mitigate their adverse effects. By
controlling gut-derived uremic toxins, patients’ cardiovascular profiles and CKD risks can be modified,
improving clinical outcomes and quality of life.
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References
Lim YJ, Sidor NA, Tonial NC, Che A, Urquhart BL. Uremic toxins in the progression of chronic kidney disease and cardiovascular disease: mechanisms and therapeutic targets. Toxins. 2021;13(2):142. doi: 10.3390/toxins13020142. DOI: https://doi.org/10.3390/toxins13020142
Veera Boopathy E, Peer Mohamed Appa MAY, Pragadeswaran S, Karthick Raja D, Gowtham M, et al. A data driven approach through IOMT based patient healthcare monitoring system. Arch Tech Sci. 2024;2(31):9-15. doi: 10.70102/afts.2024.1631.009. DOI: https://doi.org/10.70102/afts.2024.1631.009
Dalpathadu H, Salim AM, Wade A, Greenway SC. A systematic review of uremic toxin concentrations and cardiovascular risk markers in pediatric chronic kidney disease. Toxins. 2024;16(8):345. doi: 10.3390/toxins16080345. DOI: https://doi.org/10.3390/toxins16080345
Yazdkhasty A, Khorasani MSS, Bidgoli AM. Prediction of stress coping styles based on spiritual intelligence in nurses. Int Acad J Soc Sci. 2016;3(2):61-70.
Vondenhoff S, Schunk SJ, Noels H. Increased cardiovascular risk in patients with chronic kidney disease. Herz. 2024;49:95-104. doi: 10.1007/s00059-024-05235-4. DOI: https://doi.org/10.1007/s00059-024-05235-4
Martins S. Prevalence and impact of polypharmacy in elderly patients with chronic conditions. Clin J Med Health Pharm. 2025;3(2):8-13.
Rumanli Z, Vural IM, Avci GA. Chronic kidney disease, uremic toxins and microbiota. Microbiota Host. 2025. doi: 10.1530/mah-24-0012. DOI: https://doi.org/10.1530/MAH-24-0012
Das A, Kapoor S. Comprehensive review of evidence-based methods in preventive cardiology education: perspective from analytical studies. Glob J Med Terminol Res Inform. 2024;2(4):16-22.
Czaja-Stolc S, Potrykus M, Ruszkowski J, Dębska-Ślizień A, Małgorzewicz S. Nutritional status, uremic toxins, and metaboinflammatory biomarkers as predictors of two-year cardiovascular mortality in dialysis patients: a prospective study. Nutrients. 2025;17(6):1043. doi: 10.3390/nu17061043. DOI: https://doi.org/10.3390/nu17061043
Gupta N, Verma A. The role of inflammation in cardiovascular disease. Medxplore Front Med Sci. 2025:37-51.
Wang Q, Han Y, Pang L, Zhou Z, Dai L. Gut microbiome remodeling in chronic kidney disease: implications of kidney replacement therapies and therapeutic interventions. Front Med. 2025;12. doi: 10.3389/fmed.2025.1620247. DOI: https://doi.org/10.3389/fmed.2025.1620247
Luqman A, Hassan A, Ullah M, Naseem S, Ullah M, et al. Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder. Front Immunol. 2024;15. doi: 10.3389/fimmu.2024.1321395. DOI: https://doi.org/10.3389/fimmu.2024.1321395
Huang H, Chen M. Exploring the preventive and therapeutic mechanisms of probiotics in chronic kidney disease through the gut-kidney axis. J Agric Food Chem. 2024;72(15):8347-8364. doi: DOI: https://doi.org/10.1021/acs.jafc.4c00263
1021/acs.jafc.4c00263.
Wang J, Lin Y, Hsu B. Endothelial dysfunction in chronic kidney disease: mechanisms, biomarkers, diagnostics, and therapeutic strategies. Tzu Chi Med J. 2025. doi: 10.4103/tcmj.tcmj_284_24. DOI: https://doi.org/10.4103/tcmj.tcmj_284_24
Wakamatsu T, Yamamoto S, Yoshida S, Narita I. Indoxyl sulfate-induced macrophage toxicity and therapeutic strategies in uremic atherosclerosis. Toxins. 2024;16(6):254. doi: 10.3390/to xins16060254. DOI: https://doi.org/10.3390/toxins16060254
Jha PK, Nakano T, Itto LYU, Barbeiro MC, Lupieri A, et al. Vascular inflammation in chronic kidney disease: the role of uremic toxins in macrophage activation. Front Cardiovasc Med. 2025;12.
doi: 10.3389/fcvm.2025.1574489. DOI: https://doi.org/10.3389/fcvm.2025.1574489
Tsuji K, Uchida N, Nakanoh H, Fukushima K, Haraguchi S, et al. The gut-kidney axis in chronic kidney diseases. Diagnostics. 2025;15(1):21. doi: 10.3390/diagnostics15010021. DOI: https://doi.org/10.3390/diagnostics15010021
Al-Dajani AR, Hou QK, Kiang TKL. Liquid chromatography-mass spectrometry analytical methods for the quantitation of p-cresol sulfate and indoxyl sulfate in human matrices: biological applications and diagnostic potentials. Pharmaceutics. 2024;16(6):743. doi: 10.3390/pharmaceutics16060743. DOI: https://doi.org/10.3390/pharmaceutics16060743
Behrens F, Bartolomaeus H, Wilck N, Holle J. Gut-immune axis and cardiovascular risk in chronic kidney disease. Clin Kidney J.2023;17(1). doi: 10.1093/ckj/sfad303. DOI: https://doi.org/10.1093/ckj/sfad303
Renaldi R, Wiguna T, Persico AM, Tanra AJ. p-cresol and p-cresyl sulphate boost oxidative stress: a systematic review of recent evidence. Basic Clin Pharmacol Toxicol. 2025;137(1). doi: 10.1111/bcpt.70065. DOI: https://doi.org/10.1111/bcpt.70065
Frąk W, Dąbek B, Balcerczyk-Lis M, Motor J, Radzioch E, et al. Role of uremic toxins, oxidative stress, and renal fibrosis in chronic kidney disease. Antioxidants. 2024;13(6):687. doi: 10.3390/antiox13060687. DOI: https://doi.org/10.3390/antiox13060687
Lu Y, Meng L, Wang X, Zhang Y, Zhang C, Zhang M. The non-traditional cardiovascular culprits in chronic kidney disease: mineral imbalance and uremic toxin accumulation. Int J Mol Sci. 2025;26(16): 7938. doi: 10.3390/ijms26167938. DOI: https://doi.org/10.3390/ijms26167938
Cedillo-Flores R, Cuevas-Budhart MA, Cavero-Redondo I, Kappes M, Ávila-Díaz M, Paniagua R. Im-pact of gut microbiome modulation on uremic toxin reduction in chronic kidney di sease: a systematic review and network meta-analysis. Nutrients. 2025;17(7):1247. doi: 10.3390/nu17071247. DOI: https://doi.org/10.3390/nu17071247
Chermiti R, Burtey S, Dou L. Role of uremic toxins in vascular inflammation associated with chronic kidney disease. J Clin Med. 2024;13(23):7149. doi: 10.3390/jcm13237149. DOI: https://doi.org/10.3390/jcm13237149
Zwaenepoel B, De Backer T, Glorieux G, Verbeke F. Predictive value of protein-bound uremic toxins for heart failure in patients with chronic kidney disease. ESC Heart Fail. 2023;11(1):466-474.
doi: 10.1002/ehf2.14566. DOI: https://doi.org/10.1002/ehf2.14566
ISSN 2307-1257
ISSN 2307-1265
